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Depression among African Americans residing in urban communities is a complex, major public health problem; however, few studies identify early life risk factors for depression among urban African American men and women. To better inform prevention programming, this study uses data from the Woodlawn Study, a well-defined community cohort of urban African Americans followed from age 6 to 42 years, to determine depression prevalence through midlife and identify childhood and adolescent risk factors for adult depression separately by gender. Results indicate that lifetime depression rates do not differ significantly by gender (16.2 % of men, 18.8 % of women) in contrast to findings of a higher prevalence for women in national studies. Furthermore, rates of depression in this urban African American population are higher than those found in national samples of African Americans and more comparable to the higher rates found nationally among Whites. Regarding early predictors, for both men and women, family conflict in adolescence is a risk factor for adult depression in multivariate regression models. For women, vulnerability to depression has roots in early life, specifically, low maternal aspirations for school attainment. Females displaying more aggressive and delinquent behavior and those growing up in a female-headed household and a household with low maternal education have elevated rates of depression. Males growing up in persistent poverty, those engaging in greater delinquent behavior, and those with low parental supervision in adolescence also have elevated rates of depression. Effective prevention programming for urban African Americans must consider both individual characteristics and the family dynamic.